Current status of cell-based therapy for heart failure

被引:21
作者
Jakob P. [1 ,2 ]
Landmesser U. [1 ,2 ,3 ]
机构
[1] Cardiovascular Center, University Hospital Zurich, Zurich
[2] Zurich Center of Integrative Human Physiology, University Hospital Zurich, Zurich
[3] Department of Cardiology, University Hospital Zurich, 8091 Zürich
关键词
Autologous transplantation; Bone marrow transplantation; Cardiomyopathies; Heart failure; Left ventricular dysfunction; Methods; Myocardial infarction; Regeneration; Remodeling; Stem cell transplantation; Stem cells; Therapy;
D O I
10.1007/s11897-013-0134-z
中图分类号
学科分类号
摘要
In the last two decades, morbidity and mortality of patients with chronic heart failure could be further reduced by improved pharmacological and cardiac device therapies. However, despite these advances, there is a substantial unmet need for novel therapies, ideally specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature, given the limited endogenous potential for renewal of cardiomyocytes in adults. In this respect, cardiac cell-based therapies have gained substantial attention and have entered clinical feasibility and safety studies a decade ago. Different cell-types have been used, including bone marrow-derived mononuclear cells, bone marrow-derived mesenchymal stem cells, mobilized CD34+ cells, and more recently cardiac-derived c-kit+ stem cells and cardiosphere-derived cells. Some of these studies have suggested a potential of cell-based therapies to reduce cardiac scar size and to improve cardiac function in patients with ischemic cardiomyopathy. While first clinical trials examining the impact of cardiac cell-based therapy on clinical outcome have now been initiated, improved understanding of underlying mechanisms of action of cell-based therapies may lead to strategies for optimization of the cardiac repair potential of the applied cells. In experimental studies, direct in vivo reprogramming of cardiac fibroblasts towards cardiomyocytes, and microRNA-based promotion of cardiomyocyte proliferation and cardiac repair have recently been reported that may represent novel therapeutic approaches for cardiac regeneration that would not need cell-administration but rather directly stimulate endogenous cardiac regeneration. This review will focus mainly on recently completed clinical trials (within the last 2 years) investigating cardiac cell-based therapies and the current status of experimental studies for cardiac cell-based repair and regeneration with a potential for later translation into clinical studies in the future. © 2013 Springer Science+Business Media New York.
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页码:165 / 176
页数:11
相关论文
共 102 条
[1]  
Poss K.D., Wilson L.G., Keating M.T., Heart regeneration in zebrafish, Science, 298, 5601, pp. 2188-2190, (2002)
[2]  
Jopling C., Sleep E., Raya M., Marti M., Raya A., Izpisua Belmonte J.C., Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation, Nature, 464, 7288, pp. 606-609, (2010)
[3]  
Bergmann O., Bhardwaj R.D., Bernard S., Zdunek S., Barnabe-Heider F., Walsh S., Et al., Evidence for cardiomyocyte renewal in humans, Science, 324, 5923, pp. 98-102, (2009)
[4]  
Segers V.F., Lee R.T., Stem-cell therapy for cardiac disease, Nature, 451, 7181, pp. 937-942, (2008)
[5]  
Laflamme M.A., Murry C.E., Heart regeneration, Nature, 473, 7347, pp. 326-335, (2011)
[6]  
Tongers J., Losordo D.W., Landmesser U., Stem and progenitor cell-based therapy in ischaemic heart disease: Promise, uncertainties, and challenges, Eur Heart J, 32, 10, pp. 1197-1206, (2011)
[7]  
Gepstein L., Derivation and potential applications of human embryonic stem cells, Circ Res, 91, 10, pp. 866-876, (2002)
[8]  
Laflamme M.A., Chen K.Y., Naumova A.V., Muskheli V., Fugate J.A., Dupras S.K., Et al., Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts, Nat Biotechnol, 25, 9, pp. 1015-1024, (2007)
[9]  
Li Z., Wu J.C., Sheikh A.Y., Kraft D., Cao F., Xie X., Et al., Differentiation, survival, and function of embryonic stem cell derived endothelial cells for ischemic heart disease, Circulation, 116, SUPPL. 11, pp. 46-54, (2007)
[10]  
Yamashita J., Itoh H., Hirashima M., Ogawa M., Nishikawa S., Yurugi T., Et al., Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors, Nature, 408, 6808, pp. 92-96, (2000)